GPI-anchored proteins are ubiquitously expressed on the plasma membranes of eukaryotic cells. Their normal functions in humans range from the regulation of embryogenesis and lymphogenesis to protection from complement-mediated cell destruction. Pathogenic processes involving this class of proteins include disruption of cellular architecture associated with carcinogenesis, parasitic infections, and prion-associated diseases. We explored the possibility of intercellular GPI-protein transfer as a general model for intercellular communication with one eventual goal being the delivery of recombinant molecules, including proteins and nucleic acids to live cells. HeLa cells were engineered to overexpress a chimeric GPI- anchored form of the human CD4 using the transfection and transduction of recombinant adeno-associated viral vectors. Flow cytometry was used to isolate clones and monitor the stable expression level of CD4- GPI on those cells. Fluorescent-based analyses of the cell membranes and supernatants revealed CD4-GPI capable of transfer to native HeLa cells. Kinetics, temperature dependence, serum dependence, and other factors were explored to improve the efficiency and magnitude of transfer. Optimal conditions resulted in a greater than 20 fold increase in CD4 specific fluorescence relative to the negative control and the microscopic visualization of CD4-GPI aggregates on the target cells. The aggregates were sensitive to cleavage by phosphtidylinositol-specific phospholipase C. While other mechanisms may exist, a lack of cytoplasm-specific staining in the aggregates suggests GPI-proteins may transit to neighboring cells in a micellar form.